Interferon gamma production by natural killer (NK) cells and NK1.1+ T cells upon NKR-P1 cross-linking (original) (raw)

Abstract

Natural killer (NK) cells play an important role in immune response by producing interferon gamma (IFN-gamma) as well as exhibiting cytotoxic function. IFN-gamma produced by NK cells has been suggested to be involved in differentiation of T helper cells. On the other hand, the NKR-P1 molecule was recently identified as one of the important NK cell receptors, and it recognizes certain kinds of oligosaccharides on target cells and triggers NK cells for cytotoxicity. In the present study, we found that NK cells produce great amounts of IFN-gamma upon cross-linking of the NKR-P1 molecule. In contrast, stimulation of NK cells with IL-2 induced proliferation without producing IFN-gamma. Similar to NK cells, NK1.1+ T cells also produced IFN-gamma upon NKR-P1 cross-linking. NK1.1+ T cells produced IFN-gamma but not interleukin 4 (IL-4) upon NKR-P1 cross-linking, whereas they secreted both IFN-gamma and IL-4 upon T cell receptor cross-linking. These results indicate that NKR-P1 is a receptor molecule on NK and NK1.1+ T cells that induces not only cytotoxicity but also IFN-gamma production. Our findings provide a new pathway for IFN-gamma production by NK and NK1.1+ T cells through NKR-P1 molecules; it may be essential for immune regulation.

Full Text

The Full Text of this article is available as a PDF (563.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arase H., Arase-Fukushi N., Good R. A., Onoé K. Lymphokine-activated killer cell activity of CD4-CD8- TCR alpha beta + thymocytes. J Immunol. 1993 Jul 15;151(2):546–555. [PubMed] [Google Scholar]
  2. Arase H., Arase N., Kobayashi Y., Nishimura Y., Yonehara S., Onoé K. Cytotoxicity of fresh NK1.1+ T cell receptor alpha/beta+ thymocytes against a CD4+8+ thymocyte population associated with intact Fas antigen expression on the target. J Exp Med. 1994 Aug 1;180(2):423–432. doi: 10.1084/jem.180.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arase H., Arase N., Nakagawa K., Good R. A., Onoé K. NK1.1+ CD4+ CD8- thymocytes with specific lymphokine secretion. Eur J Immunol. 1993 Jan;23(1):307–310. doi: 10.1002/eji.1830230151. [DOI] [PubMed] [Google Scholar]
  4. Arase H., Arase N., Ogasawara K., Good R. A., Onoé K. An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor V beta family. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6506–6510. doi: 10.1073/pnas.89.14.6506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arase H., Arase N., Saito T. Fas-mediated cytotoxicity by freshly isolated natural killer cells. J Exp Med. 1995 Mar 1;181(3):1235–1238. doi: 10.1084/jem.181.3.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Arase H., Ono S., Arase N., Park S. Y., Wakizaka K., Watanabe H., Ohno H., Saito T. Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice. J Exp Med. 1995 Sep 1;182(3):891–895. doi: 10.1084/jem.182.3.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ballas Z. K., Rasmussen W. NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset. J Immunol. 1990 Aug 15;145(4):1039–1045. [PubMed] [Google Scholar]
  8. Bancroft G. J., Schreiber R. D., Bosma G. C., Bosma M. J., Unanue E. R. A T cell-independent mechanism of macrophage activation by interferon-gamma. J Immunol. 1987 Aug 15;139(4):1104–1107. [PubMed] [Google Scholar]
  9. Bendelac A., Killeen N., Littman D. R., Schwartz R. H. A subset of CD4+ thymocytes selected by MHC class I molecules. Science. 1994 Mar 25;263(5154):1774–1778. doi: 10.1126/science.7907820. [DOI] [PubMed] [Google Scholar]
  10. Bendelac A., Lantz O., Quimby M. E., Yewdell J. W., Bennink J. R., Brutkiewicz R. R. CD1 recognition by mouse NK1+ T lymphocytes. Science. 1995 May 12;268(5212):863–865. doi: 10.1126/science.7538697. [DOI] [PubMed] [Google Scholar]
  11. Bezouska K., Yuen C. T., O'Brien J., Childs R. A., Chai W., Lawson A. M., Drbal K., Fiserová A., Pospísil M., Feizi T. Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature. 1994 Nov 10;372(6502):150–157. doi: 10.1038/372150a0. [DOI] [PubMed] [Google Scholar]
  12. Budd R. C., Miescher G. C., Howe R. C., Lees R. K., Bron C., MacDonald H. R. Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes. J Exp Med. 1987 Aug 1;166(2):577–582. doi: 10.1084/jem.166.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chambers W. H., Vujanovic N. L., DeLeo A. B., Olszowy M. W., Herberman R. B., Hiserodt J. C. Monoclonal antibody to a triggering structure expressed on rat natural killer cells and adherent lymphokine-activated killer cells. J Exp Med. 1989 Apr 1;169(4):1373–1389. doi: 10.1084/jem.169.4.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chan S. H., Perussia B., Gupta J. W., Kobayashi M., Pospísil M., Young H. A., Wolf S. F., Young D., Clark S. C., Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869–879. doi: 10.1084/jem.173.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. D'Andrea A., Rengaraju M., Valiante N. M., Chehimi J., Kubin M., Aste M., Chan S. H., Kobayashi M., Young D., Nickbarg E. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med. 1992 Nov 1;176(5):1387–1398. doi: 10.1084/jem.176.5.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Flesch I. E., Hess J. H., Huang S., Aguet M., Rothe J., Bluethmann H., Kaufmann S. H. Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha. J Exp Med. 1995 May 1;181(5):1615–1621. doi: 10.1084/jem.181.5.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  18. Giorda R., Rudert W. A., Vavassori C., Chambers W. H., Hiserodt J. C., Trucco M. NKR-P1, a signal transduction molecule on natural killer cells. Science. 1990 Sep 14;249(4974):1298–1300. doi: 10.1126/science.2399464. [DOI] [PubMed] [Google Scholar]
  19. Hackett J., Jr, Tutt M., Lipscomb M., Bennett M., Koo G., Kumar V. Origin and differentiation of natural killer cells. II. Functional and morphologic studies of purified NK-1.1+ cells. J Immunol. 1986 Apr 15;136(8):3124–3131. [PubMed] [Google Scholar]
  20. Karlhofer F. M., Yokoyama W. M. Stimulation of murine natural killer (NK) cells by a monoclonal antibody specific for the NK1.1 antigen. IL-2-activated NK cells possess additional specific stimulation pathways. J Immunol. 1991 May 15;146(10):3662–3673. [PubMed] [Google Scholar]
  21. Lantz O., Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med. 1994 Sep 1;180(3):1097–1106. doi: 10.1084/jem.180.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. MacDonald H. R. NK1.1+ T cell receptor-alpha/beta+ cells: new clues to their origin, specificity, and function. J Exp Med. 1995 Sep 1;182(3):633–638. doi: 10.1084/jem.182.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miyatake S., Nakano H., Park S. Y., Yamazaki T., Takase K., Matsushime H., Kato A., Saito T. Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas. J Exp Med. 1995 Aug 1;182(2):401–408. doi: 10.1084/jem.182.2.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raulet D. H., Held W. Natural killer cell receptors: the offs and ons of NK cell recognition. Cell. 1995 Sep 8;82(5):697–700. doi: 10.1016/0092-8674(95)90466-2. [DOI] [PubMed] [Google Scholar]
  25. Ryan J. C., Niemi E. C., Goldfien R. D., Hiserodt J. C., Seaman W. E. NKR-P1, an activating molecule on rat natural killer cells, stimulates phosphoinositide turnover and a rise in intracellular calcium. J Immunol. 1991 Nov 1;147(9):3244–3250. [PubMed] [Google Scholar]
  26. Ryan J. C., Turck J., Niemi E. C., Yokoyama W. M., Seaman W. E. Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. J Immunol. 1992 Sep 1;149(5):1631–1635. [PubMed] [Google Scholar]
  27. Scharton T. M., Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med. 1993 Aug 1;178(2):567–577. doi: 10.1084/jem.178.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scott P., Trinchieri G. The role of natural killer cells in host-parasite interactions. Curr Opin Immunol. 1995 Feb;7(1):34–40. doi: 10.1016/0952-7915(95)80026-3. [DOI] [PubMed] [Google Scholar]
  29. Seder R. A., Paul W. E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–673. doi: 10.1146/annurev.iy.12.040194.003223. [DOI] [PubMed] [Google Scholar]
  30. Sher A., Oswald I. P., Hieny S., Gazzinelli R. T. Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha. J Immunol. 1993 May 1;150(9):3982–3989. [PubMed] [Google Scholar]
  31. Yokoyama W. M. Natural killer cell receptors. Curr Opin Immunol. 1995 Feb;7(1):110–120. doi: 10.1016/0952-7915(95)80036-0. [DOI] [PubMed] [Google Scholar]
  32. Yoshimoto T., Bendelac A., Watson C., Hu-Li J., Paul W. E. Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production. Science. 1995 Dec 15;270(5243):1845–1847. doi: 10.1126/science.270.5243.1845. [DOI] [PubMed] [Google Scholar]
  33. Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]